Abstract: Objective To analyze the spectrum and drug resistance of the pathogens in patients with postoperative infection of general surgery, and provide the basis for the rational use of antibiotics. Methods The pathogen identification and drug susceptibility test were carried out in our hospital from January 2013 to January 2016, and the source, spectrum and drug resistance of pathogens were analyzed statistically. Results A total of 589 strains were isolated from 554 patients. They were mainly from tissues (41.52%), respiratory specimens including sputum (24.55%), blood (9.75%), catheters (5.06%), peritoneal drainage and puncture fluid (4.33%), urine (4.15%), and pus (3.79%). Gram negative bacteria accounted for 74.19% of the isolated pathogens, with gram positive bacteria of 20.03% and fungi of 5.77%. Among them, Klebsiella pneumoniae and Escherichia coli were highly sensitive to imipenem and meropenem (sensibility> 95%). Pseudomonas aeruginosa was sensitive to carbapenem antibiotics (sensibility> 85%). However, acinetobacter baumannii presented drug resistance to a variety of antibiotics (drug resistance rate> 50%). Enterococcus faecalis and Enterococcus faecium were highly sensitive to vancomycin (drug resistance rate of 0%). Conclusion The surgical infection is predominantly caused by gram negative bacteria which can be treated with carbapenem antibiotics, such as meropenem.